Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus
- Author(s)
- Lee, Wen Shi; Taiaroa, George; Esterbauer, Robyn; Conlan, Meghan; Neil, Jessica A; Gartner, Matthew J; Smith, Monique; Wang, Mingyang; Shepherd, Rory A; Tran, Thomas; Pymm, Phillip; Schwab, Lara SU; Kelly, Andrew; Reilly, Ellie; Amarasena, Thakshila; Wines, Bruce D; Hogarth, PMark; Juno, Jennifer A; Kent, Stephen J; Tan, Hyon-Xhi; Subbarao, Kanta; Wheatley, Adam K;
- Details
- Publication Year 2025-04-25,Volume 3,Issue #1,Page 35
- Journal Title
- NPJ Viruses
- Abstract
- NL63 is an alphacoronavirus that uses the same ACE2 receptor as SARS-CoV and SARS-CoV-2, but generally causes mild respiratory illness. In a cohort of healthy adults, we characterised humoral responses against NL63 spike and isolated a panel of human monoclonal antibodies (mAbs), including five with potent viral neutralising activity. Four neutralising mAbs blocked ACE2 receptor engagement and were found to target the receptor binding motif. A single mAb targeting the S2 subunit displayed potent neutralisation activity comparable to those directly blocking receptor engagement. The S2 mAb targets a membrane proximal heptad repeat 2 (HR2) region in spike that is absent in betacoronaviruses, potentially revealing a site of vulnerability unique to alphacoronaviruses. For all neutralising mAbs, putative epitopes were highly conserved in over 200 NL63 sequences, including recent clinical isolates. A deeper understanding of the recognition of alphacoronavirus spike by human antibodies will guide vaccine and therapeutic development against alphacoronavirus threats.
- Publisher
- Springer Nature
- Research Division(s)
- Infection and Global Health
- Publisher's Version
- https://doi.org/10.1038/s44298-025-00116-x
- Open Access at Publisher's Site
https://doi.org/10.1038/s44298-025-00116-x- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-12-05 09:30:39
Last Modified: 2025-12-05 09:30:58